The proposed research will study the structure/function relationship of catecholamine neurotransmitters as a function of their local molecular environment. The geometrical shape or conformation of these molecules is crucial for their biological function, yet the active form of catecholamines is not known. Catecholamine levels are implicated in a variety of neurological disorders including Huntington's disease, Parkinson's disease, Alzheimer's disease and schizophrenia. Understanding the important structural parameters would be invaluable in drug design to treat such disorders. The experimental technique that will be used in these studies is high resolution laser spectroscopy in supersonic molecular beams. In molecular beans both isolated molecules and single molecules surrounded by a few solvent molecules can be studies. Gas phase studies of biological molecules in clusters is a novel approach whereby detailed molecular structures will be determined as a function of the local environment--properties inaccessible to study with solution phase techniques. The distribution of different molecular conformations is expected to vary depending on the molecular properties of the local environment. For example, in an aqueous environment, hydrogen bonding with solvent molecules will compete with intramolecular attractive interactions. In contrast, regions of the membrane where the neurotransmitter binds are known to be hydrophobic and therefore should produce different conformer populations. A hydrophobic environment can be simulated by the addition of non-polar solvent molecules. Comparison of the conformer populations in these different environments will lead to insights into the kinds of interactions that influence molecular structure. The accurate molecular geometries provided by these experiments will also be important for the evaluation of a variety of different calculational techniques currently employed in determining of structures of biological of a variety of different calculational techniques currently employed in determining of structures of biological molecular. Currently, calculated structures are used as a starting point for the complex data analysis required in high resolution spectroscopy. New methods of data analysis will be developed in the proposed research using state-of-the-are computer facilities and software development. Improvements in data analysis and laser technology will extend the range of molecules accessible with high resolution spectroscopy. The collaboration of theory and experiment on this frontier holds the promise of dramatic progress in the near future.